OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of major conduit arteries. Similarly, obesity and type 2 diabetes mellitus are associated with accumulation of macrophages in visceral white adipose tissue and pancreatic islets. Our goal was to characterize systemic inflammation in atherosclerosis with hypercholesterolemia, but without obesity. METHODS AND RESULTS: We compared 22-week-old apolipoprotein E knockout (ApoE(-/-)) with wild-type mice kept for 14 weeks on a high cholesterol (1.25%) diet (CD, n=8) and 8-week-old ApoE(-/-) with wild-type mice kept on a normal diet (ND, n=8). Hypercholesterolemic, atherosclerotic ApoE(-/-) mice on CD exhibited increased macrophages and T-cells in plaques and periadventitial adipose tissue that revealed elevated expression of MIP-1alpha, IL-1beta, IL-1 receptor, and IL-6. Mesenteric adipose tissue and pancreatic islets in ApoE(-/-) mice showed increased macrophages. Expression of IL-1beta was enhanced in mesenteric adipose tissue of ApoE(-/-) mice on CD. Furthermore, these mice exhibited steatohepatitis with macrophage and T-cell infiltrations as well as increased MIP-1alpha and IL-1 receptor expression. Blood glucose, insulin and total body weight did not differ between the groups. CONCLUSIONS: In hypercholesterolemic lean ApoE(-/-) mice, inflammation extends beyond atherosclerotic plaques to the periadventitial and visceral adipose tissue, liver, and pancreatic islets without affecting glucose homeostasis.
OBJECTIVE:Atherosclerosis is a chronic inflammatory disease of major conduit arteries. Similarly, obesity and type 2 diabetes mellitus are associated with accumulation of macrophages in visceral white adipose tissue and pancreatic islets. Our goal was to characterize systemic inflammation in atherosclerosis with hypercholesterolemia, but without obesity. METHODS AND RESULTS: We compared 22-week-old apolipoprotein E knockout (ApoE(-/-)) with wild-type mice kept for 14 weeks on a high cholesterol (1.25%) diet (CD, n=8) and 8-week-old ApoE(-/-) with wild-type mice kept on a normal diet (ND, n=8). Hypercholesterolemic, atheroscleroticApoE(-/-) mice on CD exhibited increased macrophages and T-cells in plaques and periadventitial adipose tissue that revealed elevated expression of MIP-1alpha, IL-1beta, IL-1 receptor, and IL-6. Mesenteric adipose tissue and pancreatic islets in ApoE(-/-) mice showed increased macrophages. Expression of IL-1beta was enhanced in mesenteric adipose tissue of ApoE(-/-) mice on CD. Furthermore, these mice exhibited steatohepatitis with macrophage and T-cell infiltrations as well as increased MIP-1alpha and IL-1 receptor expression. Blood glucose, insulin and total body weight did not differ between the groups. CONCLUSIONS: In hypercholesterolemic leanApoE(-/-) mice, inflammation extends beyond atherosclerotic plaques to the periadventitial and visceral adipose tissue, liver, and pancreatic islets without affecting glucose homeostasis.
Authors: Kelly J Shields; Emma Barinas-Mitchell; Matthew R Gingo; Ping Tepper; Bret H Goodpaster; Amy H Kao; Susan Manzi; Kim Sutton-Tyrrell Journal: Atherosclerosis Date: 2013-09-11 Impact factor: 5.162
Authors: Indrani Sinha-Hikim; Amiya P Sinha-Hikim; Ruoqing Shen; Hyun Ju Kim; H Kim; Samuel W French; Nosratola D Vaziri; Nosratola D Vaziri; Albert C Crum; Albert Crum; Tripathi B Rajavashisth; Keith C Norris Journal: Exp Mol Pathol Date: 2011-05-03 Impact factor: 3.362
Authors: A D Dobrian; M A Hatcher; J J Brotman; E V Galkina; P Taghavie-Moghadam; H Pei; B A Haynes; J L Nadler Journal: J Endocrinol Date: 2015-08-18 Impact factor: 4.286
Authors: Robert S Crawford; Hassan Albadawi; Alessandro Robaldo; Michael A Peck; Christopher J Abularrage; Hyung-Jin Yoo; Glenn M Lamuraglia; Michael T Watkins Journal: J Surg Res Date: 2013-03-15 Impact factor: 2.192